Our overall goal is to 1) identify a dense set of single nucleotide polymorphisms (SNPs) spanning the human genome, 2) identify two alleles at each variant site, 3) order these SNPs with high confidence on a single integrated high-resolution map of the human genome containing genes and simple sequence repeat (SSR) markers, and 4) place all of this information in a public database, accessible to a wide range of potential users. We propose a three-year collaborative effort between the Stanford Human Genome Center (SHGC) and Affymetrix, Inc. to screen 24,000 sequence tagged sites (STSs) per year for polymorphic variation using Affymetrix DNA arrays. Each STS will be derived from BAC clones and amplified from the genomic DNA of eight anonymous unrelated individuals. Our preliminary data suggest that we will identify 6,000 such polymorphisms per year, with one in every four STSs containing a common variant. We will use an independent technology (ABI gel-based fluorescent sequencing) on DNA from two informative individuals, identified by chip-based screening, to confirm each SNP. Each polymorphic allele will be placed in a publicly-accessible database within 90 days of demonstrated consistency between gel-based and chip- based analyses. Our final product will be a map of 72,000 STSs, including 18,000 SNPS, integrated with 30,000 previously-mapped genes and simple sequence repeat (SSR) markers, ordered with greater than 95 percent confidence at 100 kb resolution.